Molecular Mechanisms of Resistance to Direct-Acting Antiviral (DAA) Drugs for the Treatment of Hepatitis C Virus Infections

“…However, despite positive data regarding DAA treatment response and improved outcomes, several cases of pharmacological resistance have been described[ 9 ], making HCV infection increasingly challenging and difficult to manage. Furthermore, emerging evidence suggests a persistent risk of HCC in CHC patients post-DAAs therapy, even after achieving SVR[ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication: A systematic review and meta-analysis

Esposto,

Santini,

Galasso

et al. 2024

World J Gastroenterol

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BACKGROUND Direct-acting antiviral agents (DAAs) are highly effective treatment for chronic hepatitis C (CHC) with a significant rate of sustained virologic response (SVR). The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression. The assessment of fibrosis degree can be performed with transient elastography, magnetic resonance elastography or shear-wave elastography (SWE). Liver elastography could function as a predictor for hepatocellular carcinoma (HCC) in CHC patients treated with DAAs. AIM To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus (HCV). METHODS A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned. RESULTS At baseline and after 12 wk of follow-up, a trend was shown towards greater liver stiffness (LS) in those who go on to develop HCC compared to those who do not [baseline LS standardized mean difference (SMD): 1.15, 95% confidence interval (95%CI): 020-2.50; LS SMD after 12 wk: 0.83, 95%CI: 0.33-1.98]. The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data. There was a statistically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not (0.64; 95%CI: 0.04-1.24). CONCLUSION SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs. Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.

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“…However, it is still reported that DAA agents can cause a series of adverse events, including HBV reactivation, abnormal liver function and anemia. Meanwhile, DAA failures warrant attention, which happen with all HCV genotypes and are commonly related to the presence of HCV resistance-associated variants (RAV) 7 .…”

Section: Introductionmentioning

confidence: 99%

The prognosis associated factors of chronic hepatitis C patients and a case report of resistance-associated substitutions to sofosbuvir-velpatavir treatment

Xiong,

Pan,

Zhou

et al. 2024

Preprint

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This study retrospectively analyzed the risk factors associated with liver cancer and cirrhosis in 358 HCV infected chinese patients with positive viral load. Among them, 80 patients treated with sofosbuvir-velpatavir (SOF-VEL) were further investigated for the efficacy and safety. An unusual SOF-VEL resistance case was investigated for the resistance-associated substitutions (RAS) using next-generation sequencing. HCV genotype 1 infection (45.5%) was most prevalent in this Chinese cohort. By single and multivariate factor analyses it was found that genotype 3 infection had a poorer prognosis. Age ≥50 years, male gender, Child-Pugh Grade B and C, and FIB-4 ≥3.25 were risk factors for liver cancer, while age ≥50 years, with diabetes, and ANA positive were risk factors for cirrhosis. Treating CHC patients with SOF-VEL revealed a sustained virologic response (SVR12) rate reaching 95%. The patient who experienced response-relapses once SOF-VEL was withdrawn had a HCV genotype 2a strain infection which harbored F28S mutation in NS5A, and T273A, M289L, A421V mutations in NS5B as RAS sites. We concluded thatSOF-VEL-basedpan-genotypic direct-acting antiviral treatment for CHC patients resulted in a high rate of achieving primary endpoint. However, the patients should be carefully monitored for SVR12 after the end of treatment.

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Molecular Mechanisms of Resistance to Direct-Acting Antiviral (DAA) Drugs for the Treatment of Hepatitis C Virus Infections

Cited by 8 publications

References 66 publications

Structure-based virtual screening of unbiased and RNA-focused libraries to identify new ligands for the HCV IRES model system

Structure-based virtual screening of unbiased and RNA-focused libraries to identify new ligands for the HCV IRES model system

Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication: A systematic review and meta-analysis

The prognosis associated factors of chronic hepatitis C patients and a case report of resistance-associated substitutions to sofosbuvir-velpatavir treatment

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